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Q4KSH7 (MP2K7_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 58. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Dual specificity mitogen-activated protein kinase kinase 7
Short name=MAP kinase kinase 7
Short name=MAPKK 7
EC=2.7.12.2
Alternative name(s):
JNK-activating kinase 2
MAPK/ERK kinase 7
Short name=MEK 7
c-Jun N-terminal kinase kinase 2
Short name=JNK kinase 2
Short name=JNKK 2
Gene names
Name:Map2k7
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length419 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Ref.2

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.2

Cofactor

Magnesium. Ref.2

Enzyme regulation

Activated by phosphorylation by specific MAP kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3 and MAP3K12/DLK. UniProtKB O14733 UniProtKB Q8CE90

Subunit structure

Interacts with VRK2 By similarity. Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1 and MAP3K1/MEKK1. Interacts with MAPK8IP1/JIP1, MAPK8IP2/JIP2 and MAPK8IP3/JIP3 scafforld proteins By similarity. Ref.3

Subcellular location

Nucleus. Cytoplasm By similarity UniProtKB Q8CE90.

Domain

The DVD domain (redidues 377-400) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.

The D domain (redidues 37-57) contains a conserved docking site and is required for the binding to MAPK substrates.

Post-translational modification

Activated by phosphorylation on Ser-271 and Thr-275 by MAP kinase kinase kinases (MAP3Ks).

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 419418Dual specificity mitogen-activated protein kinase kinase 7
PRO_0000271407

Regions

Domain120 – 380261Protein kinase
Nucleotide binding126 – 1349ATP By similarity UniProtKB Q13131
Region37 – 5721D Domain By similarity
Region377 – 40024DVD domain By similarity
Coiled coil2 – 3029 Potential

Sites

Active site2431Proton acceptor By similarity UniProtKB Q13131
Binding site1491ATP By similarity UniProtKB Q13131
Site44 – 452Cleavage; by anthrax lethal factor By similarity UniProtKB O14733
Site76 – 772Cleavage; by anthrax lethal factor By similarity UniProtKB O14733

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue2711Phosphoserine; by MAP3K By similarity
Modified residue2751Phosphothreonine; by MAP3K By similarity

Sequences

Sequence LengthMass (Da)Tools
Q4KSH7 [UniParc].

Last modified August 2, 2005. Version 1.
Checksum: 60405BF7111E294B

FASTA41947,536
        10         20         30         40         50         60 
MAASSLEQKL SRLEAKLKQE NREARRRIDL NLDISPQRPR PTLQLPLAND GGSRSPSSES 

        70         80         90        100        110        120 
SPQHPTPPSR PRHMLGLPST LFTPRSMESI EIDQKLQEIM KQTGYLTIGG QRYQAEINDL 

       130        140        150        160        170        180 
ENLGEMGSGT CGQVWKMRFR KTGHIIAVKQ MRRSGNKEEN KRILMDLDVV LKSHDCPYIV 

       190        200        210        220        230        240 
QCFGTFITNT DVFIAMELMG TCAEKLKKRM QGPIPERILG KMTVAIVKAL YYLKEKHGVI 

       250        260        270        280        290        300 
HRDVKPSNIL LDERGQIKLC DFGISGRLVD SKAKTRSAGC AAYMAPERID PPDPTKPDYD 

       310        320        330        340        350        360 
IRADVWSLGI SLVELATGQF PYKNCKTDFE VLTKVLQEEP PLLPGHMGFS GDFQSFVKDC 

       370        380        390        400        410 
LTKDHRKRPK YNKLLEHSFI KHYETLEVDV ASWFKDVMAK TESPRTSGVL SQHHLPFFR

« Hide

References

[1]Itoh T., Horiuchi M., Itoh A.
Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
[2]"Stress- and cell type-dependent regulation of transfected c-Jun N-terminal kinase and mitogen-activated protein kinase kinase isoforms."
Butterfield L., Zentrich E., Beekman A., Heasley L.E.
Biochem. J. 338:681-686(1999) [PubMed: 10051439] [Abstract]
Cited for: FUNCTION.
[3]"Delayed activation and regulation of MKK7 in hippocampal CA1 region following global cerebral ischemia in rats."
Zhang Q., Tian H., Fu X., Zhang G.
Life Sci. 74:37-45(2003) [PubMed: 14575811] [Abstract]
Cited for: PHOSPHORYLATION, INTERACTION WITH MAPK8/JNK1; MAPK9/JNK2; MAPK10/JNK3; MAP3K11/MLK3 AND MAP3K5/ASK1.
[4]"Differential regulation and properties of MAPKs."
Raman M., Chen W., Cobb M.H.
Oncogene 26:3100-3112(2007) [PubMed: 17496909] [Abstract]
Cited for: REVIEW ON ENZYME REGULATION.
[5]"Diverse physiological functions of MKK4 and MKK7 during early embryogenesis."
Asaoka Y., Nishina H.
J. Biochem. 148:393-401(2010) [PubMed: 20801953] [Abstract]
Cited for: REVIEW ON FUNCTION.
[6]"The bottleneck of JNK signaling: molecular and functional characteristics of MKK4 and MKK7."
Haeusgen W., Herdegen T., Waetzig V.
Eur. J. Cell Biol. 90:536-544(2011) [PubMed: 21333379] [Abstract]
Cited for: REVIEW ON REGULATION, REVIEW ON FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AY879265 mRNA. Translation: AAX61178.1.
IPIIPI00779757.
RefSeqNP_001020596.1. NM_001025425.1.
UniGeneRn.162081.

3D structure databases

HSSPHSSP built from PDB template 1S9I based on UniProtKB P36507.
ProteinModelPortalQ4KSH7.
SMRQ4KSH7. Positions 103-402.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ4KSH7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID363855.
KEGGrno:363855.
UCSCNM_001025425. rat.

Organism-specific databases

CTD5609.
RGD1560043. Map2k7.

Phylogenomic databases

eggNOGroNOG15478.
GeneTreeENSGT00570000078767.
HOVERGENHBG108518.
PhylomeDBQ4KSH7.

Gene expression databases

ArrayExpressQ4KSH7.
GenevestigatorQ4KSH7.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR002290. Ser/Thr_kinase_dom.
[Graphical view]
KOK04431.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. Kinase_like. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio684348.

Entry information

Entry nameMP2K7_RAT
AccessionPrimary (citable) accession number: Q4KSH7
Entry history
Integrated into UniProtKB/Swiss-Prot: January 9, 2007
Last sequence update: August 2, 2005
Last modified: January 25, 2012
This is version 58 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

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